Vitamin B12, in the form of its coenzyme, is a cofactor for a series of eleven enzyme catalyzed transformations. Of these, three enzymes: beta-methylaspartate mutase, methylmalonyl-SCoA mutase and methylitaconate mutase are of special interest because they catalyze carbon skeleton rearrangements, for which there has been no analogue in organic chemistry. In this proposal, we present two new chemical model reactions in which methylitaconate and methylmalonate, attached through their methyl groups to the cobalt atom of vitamin B12, have been found to rearrange spontaneously to alpha-methyleneglutarate and succinate, respectively. This is the first observation of a B12 dependent rearrangement occurring in the absence of enzyme. This result signals a much stronger chemical and biochemical role for coenzyme B12 than has hitherto been imagined possible. It is proposed to take advantage of this discovery in several crucial areas. Isotopic labelling studies and determination of the absolute configuration of the rearrangement reaction will be used to establish the extent of congruence between the model reactions and their enzyme catalyzed counterparts. Other square-planar cobalt complexes, including degradation products of vitamin B12, will be examined in an effort to determine the limits of activity, as it is related to structure. Possible intermediates in the model reactions will be tested using electron spin resonance spectroscopy and ultraviolet spectroscopy, and chemical trapping techniques. Synthesis of a model for the beta-methylasparate rearrangement will be proposed and a novel model for the hydrogen abstraction reaction will be investigated. Preparation of simple alpha-methylene lactones is discussed.